Finasteride: Does it affect spermatogenesis and pregnancy?

Meena Pole, MD Gideon Koren, MD, FRCPC

December, 2001

ABSTRACT

QUESTION

A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets?

ANSWER

To date, there are no reports of adverse pregnancy outcomes among women exposed to finasteride. Taking 1 mg of finasteride daily did not have any clinically significant effect on menÕs semen. Absorption through the skin while handling tablets is extremely unlikely to cause fetal exposure or harm. There is no reason to discontinue the drug. Motherisk is currently following up women who are pregnant or planning pregnancy and whose partners are taking finasteride.

Finasteride, an oral type II 5-reductase inhibitor, selectively
blocks androgen activity in the prostate and skin and hence is
potentially useful for treating male pattern baldness, hirsutism, and
acne.1 Hirsute womenÕs skin shows heightened 5-reductase activity,2 so finasteride could be used to treat them also.

Finasteride, a potent competitive 5-reductase inhibitor, reduces testosterone metabolism to dihydrotestosterone (DHT).1,3
This is an important step because baldness is not known to occur unless
testosterone is converted to dihydrotestosterone. Finasteride decreases
circulating DHT without decreasing testosterone.3

Dihydrotestosterone is responsible for acne, increases of body
and facial hair during puberty, prostate gland growth, and development
of male genitalia in utero. Use of finasteride is, therefore,
contraindicated for pregnant women or women trying to become pregnant.1

Risk of exposure Finasteride is absorbed mainly from
the gastrointestinal tract, is not affected by food, and has a
bioavailability ranging from 60% to 80%. It is highly bound to protein
and undergoes extensive metabolism by hepatic cytochrome P-450 enzymes.
It is mainly eliminated through bile and feces (60% to 80%) with
minimal renal excretion (no dose adjustment is needed for elderly
patients or patients with renal impairment). Its mean serum half-life
ranges from 4.7 to 7.1 h but, because its biologic half-life is much
longer, DHT might be suppressed for nearly 2 weeks after discontinuing
it.3

In one study, semen levels were measured in 35 men taking 1 mg of finasteride daily for 6 weeks.4
Highest level measured was 1.52ng/mL; mean level was 0.26 ng/mL.
Assuming a 100% vaginal absorption through a 5-mL ejaculate per day,
women would be exposed to 7.6ng/d, a negligible amount. This level is
750 times lower than the Òno effectÓ level for developmental
abnormalities in rhesus monkeys.4Consequences of exposure Similarly, animal studies conducted
by the drugÕs manufacturer of giving 800 ng/d of finasteride
intravenously (750 times the highest estimated exposure of pregnant
women from semen of men taking 1 mg/d) to monkeys found no
abnormalities among male fetuses.4
To confirm the relevance of results in rhesus monkeys for human fetal
development, pregnant monkeys were administered high oral doses of
finasteride (2 mg/kg/d, which is equivalent to 100 times the
recommended human dose of 1 mg/d, or 12 million times the highest
estimated exposure from semen of men taking 1amg/d). Results showed
abnormalities in male external genitalia, but no other abnormalities
and no effect on female fetuses.

In 1999, a double-blind, randomized placebo-controlled
multicentre study was conducted on 181 men between 19 and 41 years old.
These men received 1 mg/d of finasteride or placebo for 48 weeks (4
spermatogenic cycles) and no drugs for the following 60 weeks. Among
these 181 men, 79 were included in a supset for collection and analysis
of sequential semen samples. Results showed that 1 mg/d of finasteride
did not have any significant effect on sperm concentration, total sperm
per ejaculate, or sperm motility or morphology.5

The absence of clinically significant effects of 1 mg/d of
finasteride on semen parameters supports the hypothesis that
testosterone and not DHT is the primary androgen regulating
spermatogenesis, sperm maturation, and seminal fluid production.4,5
Similarly, men with 5-reductase deficiency have lifelong (including in
utero) suppression of DHT formation, with low serum DHT levels and
mildly elevated testosterone levels. Their other morphologic features
include rudimentary prostates, small seminal vesicles, normal
epididymal size, and markedly diminished volume of ejaculate.6,7

The notable decrease in volume of ejaculate in these men was
attributed to in utero reduction of DHT, which led to development of a
rudimentary prostate gland. In the absence of any other anatomic
abnormalities, these men have been shown to have normal spermatogenesis
and healthy progeny.6-9 Side effects reported with
finasteride were mainly related to sexual dysfunction; effects were
mild and disappeared after treatment was discontinued.3

Women also become alarmed after reading finasterideÕs label or
product monograph. They are afraid to handle crushed or broken tablets,
especially during pregnancy.4 Tablets, however, are coated with film,
so risk of absorption of finasteride through the skin is negligible and
is unlikely to cause harm to a fetus.

No drug interactions have been reported with finasteride.
Hirsute women taking oral contraceptives who were treated with
finasteride showed a marked elevation in serum cholesterol levels.
Finasteride alone did not produce this effect.10

In the future, finasteride could be used to treat acne and hirsutism in women.10,11
Women using finasteride should be advised to use contraception to avoid
pregnancy and hence the risk of feminization of male fetusesÕ external
genitalia. To date, no study has explored the effect of 5-reductase
inhibitors on hirsute patients.

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The following corporations have provided financial support of $5,000 or more to Motherisk Programs and/or research since 2011: Beer Canada, Duchesnay, LCBO, Novartis, UCB and Shoppers Drug Mart. Funding from these organizations and their customers support Motherisk's research, helplines and other activities, but are not associated with the Motherisk Drug Testing Laboratory.

In addition, Dr. Gideon Koren, founding Director of Motherisk, acted as a consultant to Bayer, Novartis and Duchesnay during this time period.

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